Polyhedron 29 (2010) 2142–2148

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Polyhedron

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New phosphoroamidate compounds: Synthesis, structural characterizationand studies on ZnCl2 assisted hydrolysis of the P–N bond

Payal Malik, Debashis Chakraborty *, Venkatachalam RamkumarDepartment of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, Tamil Nadu, India

a r t i c l e i n f o

Article history:Received 16 November 2009Accepted 8 April 2010Available online 24 April 2010

Keywords:PhosphorodichloridateDibenzylphosphorodiamidateZinc chlorideHydrolysisHexamethylphosphoramide

0277-5387/$ - see front matter � 2010 Elsevier Ltd. Adoi:10.1016/j.poly.2010.04.002

* Corresponding author. Tel.: +91 44 22574223; faxE-mail address: dchakraborty@iitm.ac.in (D. Chakr

a b s t r a c t

A variety of phosphorodiamidate compounds were synthesized from the corresponding phosphorodi-chloridate intermediates and phosphorus oxychloride. These were completely characterized usingdifferent spectroscopic methods and single crystal X-ray diffraction studies on one of them. Studiesrevealed that water in the presence of a mild Lewis acid like ZnCl2 was found to assist the hydrolysisof the P–N linkage. The proof of this concept was effectively realized through the hydrolysis ofhexamethylphosphoramide.

� 2010 Elsevier Ltd. All rights reserved.

1. Introduction

Organophosphorus chemistry is indeed intriguing and spans avariety of research areas which include chemical synthesis, studieson their coordination chemistry with different metals and theirrole in biomedicine [1]. The chemistry of organophosphorus com-pounds has been a popular research area because of their applica-tions in agriculture [2], pharmaceuticals [3–8], biology [9,10] andchemical agents [11–17]. Organic phosphines, phosphites, phos-phinites and amidophosphinites are widely used in homogeneouscatalysis as ligands in transition-metal complexes. The very exis-tence of this area, which is of primary importance in today’s chem-istry, especially in its infancy, was due to the use of phosphinecomplexes of palladium, platinum, rhodium, etc. The use of transi-tion-metal complexes with chiral phosphine ligands [18–20] ascatalysts is of particular interest when performing asymmetrichydrogenation, hydroformylation and many other reactions. Thesecatalysts enabled the syntheses of enantiomerically pure com-pounds, including the most important pharmaceutical derivatives.Phosphorus containing polymers possess valuable properties, suchas fire resistance and inertness to chemical reagents, which makethem interesting from a practical point of view [21,22]. Organo-phosphorus compounds find extensive use in synthetic organicchemistry. This primarily includes well-known olefination reac-tions: Wittig reaction and P–O olefination that is, the reaction ofphosphorus-containing carbanions with carbonyl compounds(Horner–Woodward–Emmons reaction) [23]. Some organophos-

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: +91 44 22574202.aborty).

phonic acids have been implicated as insecticides and sterilizingagents [24] whereas diphosphonic acids have been found usefulfor anti inflammatory and pain easing activities [25]. Phosphoram-idate compounds containing N-phosphorylated amino acids havebeen particularly useful for their antiviral, antitumor and antiHIV properties [26–29]. Quantum chemical calculations on theirstructure [30,31] and spectroscopic properties [32–34] of thesehave revealed interesting conclusions. We were inspired to ventureinto the chemistry of phosphorodiamidates for their potential useas ligands in the coordination chemistry with transition-metals[35–38]. In this regard, we have developed a general route towardsthe synthesis of various N,N0-dibenzylphosphorodiamidates. Thesecompounds were anticipated to provide bidentate ligating envi-ronment with different metal synthons. However, the P–N bondis moderately polar and susceptible to attack by nucleophiles. Asimple nucleophile like water in the presence of a mild Lewis acidlike ZnCl2 was found to cleave this linkage. The work presented is areflection of our understanding in this context.

2. Experimental

2.1. General methods

The reactions concerning the synthesis of phosphorodichlori-dates and phosphoroamidates were performed under dry argonatmosphere using standard Schlenk techniques with rigorousexclusion of moisture and air. Toluene and tetrahydrofuran (THF)were dried by heating under reflux over sodium and benzophe-none and distilled fresh prior to use. All the phenols used in this

P. Malik et al. / Polyhedron 29 (2010) 2142–2148 2143

study along with phosphorous oxychloride, hexamethylphospho-ramide (HMPA) and zinc chloride were purchased from Aldrichand used without subsequent purification. Toluene, hexane, ethylacetate, methylene chloride, chloroform and tetrahydrofuran werepurchased from Ranchem India. CDCl3 used for NMR spectral mea-surements was purchased from Aldrich. For the spectral character-ization of phosphorodichloridates, the CDCl3 used was dried overcalcium hydride and distilled.

2.2. Instrumentation

1H and 13C NMR spectra were recorded with a Bruker Avance400 instrument. Chemical shifts for 1H and 13C NMR spectra werereferenced to residual solvent resonances and are reported as partsper million relative to SiMe4. 31P NMR spectra were recorded rela-tive to 85% H3PO4 as an external standard. Mass spectra of the sam-ple were recorded on a Micro mass QToF instrument, lowresolution electro-spray ionization (ESI) mass spectrometer usingmethanol solvent. GC–MS were recorded using Jeol JMS GC-MateII instrument. Infrared spectra were recorded using a Nicolet6700 FTIR instrument. Elemental analyses were done with a PerkinElmer Series 11 analyzer.

2.3. Synthesis of phosphorodichloridates (1–5)

The required phenol was stirred under reflux with phosphorousoxychloride in the stoichiometric ratio 1:4 and catalytic amount oflithium chloride. The reaction was monitored using TLC (5% ethylacetate in hexane) against the required phenol. The time requiredfor completion of the reaction was found to be 24 h for 1, 4 and 5and 48 h for 2 and 3. The reaction mixture was purified by distillingthe excess POCl3 under reduced pressure to yield the phosphorod-ichloridates as colorless viscous liquids.

2.3.1. 2-MeC6H4OP(O)Cl2 (1)The compound 1 was synthesized from 2-MeC6H4OH (1.0 g,

9.2 mmol), POCl3 (5.6 g, 36.8 mmol) and LiCl (8.7 mg, 0. 2 mmol).Yield = 1.2 g (56%). 1H NMR (400 MHz, CDCl3, ppm): d 7.34–7.20(m, 4H, ortho, meta, para), 2.35 (s, 3H, ArMe). 13C NMR (100 MHzCDCl3, ppm): d 148.84 (Ar–O), 132.03 (Ar–C), 129.49 (Ar–C),127.43 (Ar–Me), 126.94 (Ar–C), 120.04 (Ar–C), 16.32 (Ar–Me).31P{1H} NMR (161 MHz CDCl3, ppm): d 3.44 (s). GC–MS: 224.76(M+H)+. Anal. Calc. for C7H7Cl2O2P: C, 37.37; H, 3.14. Found: C,37.54; H, 3.08%.

2.3.2. 2-FC6H4OP(O)Cl2 (2)The compound 2 was synthesized from 2-FC6H4OH (1.0 g,

8.9 mmol), POCl3 (5.5 g, 35.6 mmol) and LiCl (8.4 mg, 0. 2 mmol).Yield = 1.1 g (50%). 1H NMR (400 MHz, CDCl3, ppm): d 7.43–7.17(m, 4H, ortho, meta, para). 13C NMR (100 MHz CDCl3, ppm): d154.65 (Ar–F), 148.80 (Ar–O), 128.44 (Ar–C), 125.12 (Ar–C),122.84 (Ar–C), 117.74 (Ar–C). 31P{1H} NMR (161 MHz CDCl3,ppm): d 3.01 (s). GC–MS: 228.15 (M+H)+. Anal. Calc. forC6H4Cl2FO2P: C, 31.47; H, 1.76. Found: C, 31.68; H, 1.44%.

2.3.3. 2-ClC6H4OP(O)Cl2 (3)The compound 3 was synthesized from 2-ClC6H4OH (1.0 g,

7.8 mmol), POCl3 (4.8 g, 31.2 mmol) and LiCl (8.4 mg, 0.2 mmol).Yield = 1 g (50%). 1H NMR (400 MHz, CDCl3, ppm): d 7.51–7.28(m, 4H, ortho, meta, para). 13C NMR (100 MHz CDCl3, ppm): d145.94 (Ar–O), 131.27 (Ar–C), 128.28 (Ar–C), 127.97 (Ar–Cl),125.92 (Ar–C), 121.92 (Ar–C). 31P{1H} NMR (161 MHz CDCl3,ppm): d 4.05 (s). GC–MS: 245.06 (M+H)+. Anal. Calc. forC6H4Cl3O2P: C, 29.36; H, 1.64. Found: C, 29.65; H, 1.77%.

2.3.4. 4-MeC6H4OP(O)Cl2 (4)The compound 4 was synthesized from 4-MeC6H4OH (1.0 g,

9.2 mmol), POCl3 (5.6 g, 36.8 mmol) and LiCl (8.7 mg, 0.2 mmol).Yield = 1.3 g (60%). 1H NMR (400 MHz, CDCl3, ppm): d 7.18–7.14(m, 4H, ortho, meta), 2.31 (s, 3H, ArMe). 13C NMR (100 MHz CDCl3,ppm): d 147.57 (Ar–O), 137.06 (Ar–C), 130.75 (Ar–Me), 120.30 (Ar–C), 20.76 (Ar–Me). 31P{1H} NMR (161 MHz CDCl3, ppm): d 3.57 (s).GC–MS: 224.30 (M+H)+. Anal. Calc. for C7H7Cl2O2P: C, 37.37; H,3.14. Found: C, 37.51; H, 3.22%.

2.3.5. 4-t-BuC6H4OP(O)Cl2 (5)The compound 5 was synthesized from 4-tBuC6H4OH (1.0 g,

6.8 mmol), POCl3 (4.2 g, 27.2 mmol) and LiCl (8.4 mg, 0.2 mmol).Yield = 1.1 g (62%). 1H NMR (400 MHz, CDCl3, ppm): d 7.43 (d,2H, meta), 7.19 (d, 2H, ortho), 1.31 (s, 9H, Ar–CMe3). 13C NMR(100 MHz CDCl3, ppm): d 150.21 (Ar–O), 147.38 (Ar–CMe3),127.03 (Ar–C), 119.84 (Ar–C), 34.55 (CMe3), 31.29 (CMe3). 1P{1H}NMR (161 MHz CDCl3, ppm): d 3.59 (s). GC–MS: 267.36 (M+H)+.Anal. Calc. for C10H13Cl2O2P: C, 44.97; H, 4.91. Found: C, 45.26; H,4.69%.

2.4. Synthesis of N,N0-dibenzylphosphorodiamidates (6–10)

An aryl phosphorodichloridate and benzylamine in a stoichiom-etric ratio 1:4 were stirred for 12 h in toluene (10 mL) underambient conditions to produce the corresponding N,N0-dibenzyl-phosphorodiamidate. The reaction mixture was quenched withwater and extracted with methylene chloride. Removal of the vol-atiles gave the crude product which was subsequently purified bycolumn chromatography (70% of chloroform in hexane as eluent)and obtained as a white solid after removal of volatiles.

2.4.1. 2-MeC6H4OP(O)(NHBn)2 (6) (Bn = PhCH2–)The compound 6 was synthesized from 1 (0.45 g, 2 mmol) and

BnNH2 (0.86 g, 8 mmol). Yield = 0.4 g (60%). M.p. = 53 �C. IR (neat,cm�1): 3377 (N–H), 1223 (P@O), 697 (P–N). 1H NMR (400 MHz,CDCl3, ppm): d 7.44–7.06 (m, 14H, ortho, meta, para), 4.21 (m,4H, CH2Bn), 3.22 (br, 2H, NH), 2.23 (s, 3H, ArMe). 13C NMR(100 MHz CDCl3, ppm): d 149.79 (Ar–O), 139.64 (Ar–C), 129.03(Ar–C), 128.40 (Ar–C), 127.36 (Ar–C), 127.28 (Ar–C), 127.19 (Ar–Me), 126.90 (Ar–C), 124.11 (Ar–C), 119.83 (Ar–C), 45.25 (CH2Ph),16.50 (Ar–Me). 31P{1H} NMR (161 MHz CDCl3, ppm): d 10.96. HRMS(ESI) for C21H23N2O2P (M+H)+: Calc., 367.1575; Found: 367.1577.

2.4.2. 2-FC6H4OP(O)(NHBn)2 (7)The compound 7 was synthesized from 2 (0.46 g, 2 mmol) and

BnNH2 (0.86 g, 8 mmol). Yield = 0.4 g (53%). M.p. = 48 �C. IR (neat,cm�1): 3199 (N–H), 1260 (P@O), 692 (P–N). 1H NMR (400 MHz,CDCl3, ppm): d 7.38–7.05 (m, 14H, ortho, meta, para), 4.18 (m,4H, CH2Bn), 3.05 (br, 2H, NH). 13C NMR (100 MHz CDCl3, ppm): d158.23 (Ar–F), 155.17 (Ar–O), 139.49 (Ar–C), 128.77 (Ar–C),127.50 (Ar–C), 125.49 (Ar–C), 124.73 (Ar–C), 123.30 (Ar–C),116.86 (Ar–C), 45.35 (CH2Ph). 31P{1H} NMR (161 MHz CDCl3,ppm): d 11.24. HRMS (ESI) for C20H20FN2O2P (M+Na)+: Calc.,393.1144; Found: 393.1140.

2.4.3. 2-ClC6H4OP(O)(NHBn)2 (8)The compound 8 was synthesized from 3 (0.49 g, 2 mmol) and

BnNH2 (0.86 g, 8 mmol). Yield = 0.4 g (51%). M.p. = 70 �C. IR (neat,cm�1): 3229 (N–H), 1259 (P@O), 702 (P–N). 1H NMR (400 MHz,CDCl3, ppm): d 7.57–7.13 (m, 14H, ortho, meta, para), 4.24 (m,4H, CH2Bn), 3.17 (br, 2H, NH). 13C NMR (100 MHz CDCl3, ppm): d146.92 (Ar–O), 138.75 (Ar–C), 130.68 (Ar–C), 128.71 (Ar–C),128.07 (Ar–C), 127.66 (Ar–C), 127.53 (Ar–C), 126.04 (Ar–Cl),125.79 (Ar–C), 122.03 (Ar–C), 45.91 (CH2Ph). 31P{1H} NMR

2144 P. Malik et al. / Polyhedron 29 (2010) 2142–2148

(161 MHz CDCl3, ppm): d 11.09. HRMS (ESI) for C20H20ClN2O2P(M+Na)+: Calc., 409.0849; Found: 409.0845.

2.4.4. 4-MeC6H4OP(O)(NHBn)2 (9)The compound 9 was synthesized from 4 (0.45 g, 2 mmol) and

BnNH2 (0.86 g, 8 mmol). Yield = 0.5 g (63%). M.p. = 65 �C. IR (neat,cm�1): 3198 (N–H), 1200 (P@O), 690 (P–N). 1H NMR (400 MHz,CDCl3, ppm): d 7.31–7.10 (m, 14H, ortho, meta, para), 4.18 (m,4H, CH2Bn), 2.98 (br, 2H, NH), 2.31 (s, 3H, ArMe). 13C NMR(100 MHz CDCl3, ppm): d 148.89 (Ar–O), 139.58 (Ar–C), 134.18(Ar–Me), 130.23 (Ar–C), 128.74 (Ar–C), 127.61 (Ar–C), 120.23(Ar–C), 45.39 (CH2Ph), 20.83 (Ar–Me). 31P{1H} NMR (161 MHzCDCl3, ppm): d 10.96. HRMS (ESI) for C21H23N2O2P (M+H)+: Calc.,367.1575; Found: 367.1581.

2.4.5. 4-t-BuC6H4OP(O)(NHBn)2 (10)The compound 10 was synthesized from 5 (0.53 g, 2 mmol) and

BnNH2 (0.86 g, 8 mmol). Yield = 0.6 g (72%). M.p. = 40 �C. IR (neat,cm�1): 3174 (N–H), 1203 (P@O), 690 (P–N). 1H NMR (400 MHz,CDCl3, ppm): d 7.24–7.05 (m, 14H, ortho, meta, para), 4.11 (m,4H, CH2Bn), 2.79 (br, 2H, NH), 1.25 (s, 9H, Ar–CMe3). 13C NMR(100 MHz CDCl3, ppm): d 148.79 (Ar–O), 147.46 (Ar–CMe3),139.61 (Ar–C), 128.71 (Ar–C), 127.62 (Ar–C), 127.45 (Ar–C),126.63 (Ar–C), 119.90 (Ar–C), 45.38 (CH2Ph), 34.46 (Ar–CMe3),31.55 (Ar–CMe3). 31P{1H} NMR (161 MHz CDCl3, ppm): d 11.25.HRMS (ESI) for C24H29N2O2P (M+H)+: Calc., 409.2045; Found:409.2048.

2.5. Synthesis of 4-t-Buphenyl N,N0-di–methylbenzylphosphorodi-amidate (11)

A stirred solution of 5 (1.34 g, 5 mmol) in 10 mL toluene was re-acted with (±)-a-methylbenzylamine (3.03 g, 25 mmol) underambient conditions for 12 h. The reaction mixture was quenchedwith water and extracted with methylene chloride. Removal ofthe volatiles gave the crude product which was subsequently puri-fied by column chromatography (60% of chloroform in hexane aseluent) and obtained as a colorless viscous solid after removal ofvolatiles.

Yield = 1.8 g (81%). IR (neat, cm�1): 3199 (N–H), 1213 (P@O),696 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d 7.29–6.99 (m, 14H,ortho, meta, para), 4.53 (q, 2H, CHMe), 3.18 (br, 1H, NH), 2.99 (br,1H, NH), 1.43 (d, 6H, CHMe), 1.30 (s, 9H, ArtBu). 13C NMR(100 MHz CDCl3, ppm): d 148.95 (Ar–O), 147.01 (Ar–CMe3),145.17 (Ar–C), 128.62 (Ar–C), 127.09 (Ar–C), 126.38 (Ar–C),125.94 (Ar–C), 119.78 (Ar–C), 51.39 (CHMe), 34.36 (Ar–CMe3),31.53 (Ar–CMe3), 25.34 (CHMe). 31P{1H} NMR (161 MHz CDCl3,ppm): d 8.70. HRMS (ESI) for C26H33N2O2P (M+H)+: Calc.,437.2358; Found: 437.2355.

2.6. Synthesis of phosphonic acid anion (12–17)

To a stirred solution of N,N0-dibenzylphosphorodiamidate/HMPA in THF (10 mL) was added ZnCl2 under ambient conditionsin a stoichiometric ratio 1:1. The time required for completion ofthe reaction was found to be 12 h for 12, 15–17 and 24 h for 13and 14. The solvent was removed under reduced pressure andthe reaction mixture was extracted with toluene and subsequentlyfiltered. Evaporation of the solvent yielded the crude productwhich was purified by crystallization from 1:1 methylene chlorideand hexane mixture at 0 �C.

2.6.1. [2-MeC6H4OP(O)O(OH)][BnNH3] (12)The compound 12 was synthesized from 6 (0.10 g, 0.23 mmol)

and ZnCl2 (37 mg). Yield = 42 mg (70%). IR (neat, cm�1): 3306 (N–H), 1223 (P@O), 696 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d

7.33–7.11 (m, 9H, ortho, meta, para), 4.21 (m, 2H, CH2Ph), 3.89 (s,5H, THF and OH), 2.15 (s, 3H, Ar–Me), 1.90 (s, 4H, THF). 13C NMR(100 MHz CDCl3, ppm): d 148.84 (Ar–O), 138.34 (Ar–C), 131.63(Ar–C), 128.88 (Ar–C), 128.77 (Ar–C), 127.69 (Ar–C), 127.38 (Ar–C), 127.30 (Ar–Me), 125.26 (Ar–C), 119.83 (Ar–C), 69.28 (THF),45.32 (CH2Ph), 25.48 (THF), 16.62 (Ar–Me). 31P{1H} NMR(161 MHz CDCl3, ppm): d 13.18. HRMS (ESI) for C14H18NO4P(M+THF)+: Calc., 367.1549; Found: 367.1553.

2.6.2. [2-FC6H4OP(O)O(OH)][BnNH3] (13)The compound 13 was synthesized from 7 (0.10 g, 0.27 mmol)

and ZnCl2 (36 mg). Yield = 56 mg (70%). IR (neat, cm�1): 3302 (N–H), 1202 (P@O), 693 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d7.29–7.09 (m, 9H, ortho, meta, para), 4.19 (m, 2H, CH2Ph), 3.91(br, 1H, OH). 13C NMR (100 MHz CDCl3, ppm): d 151.01 (Ar–F),138.48 (Ar–O), 138.42 (Ar–C), 128.81 (Ar–C), 127.69 (Ar–C),126.26 (Ar–C), 125.01 (Ar–C), 123.29 (Ar–C), 116.89 (Ar–C), 45.26(CH2Ph). 31P{1H} NMR (161 MHz CDCl3, ppm): d 13.75. HRMS(ESI) for C13H15FNO4P (M+THF)+: Calc., 371.1298; Found: 371.1290.

2.6.3. [2-ClC6H4OP(O)O(OH)][BnNH3] (14)The compound 14 was synthesized from 8 (0.10 g, 0.25 mmol)

and ZnCl2 (35 mg). Yield = 55 mg (70%). IR (neat, cm�1): 3378 (N–H), 1260 (P@O), 692 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d7.43–7.10 (m, 9H, ortho, meta, para), 5.05 (s, 1H, OH), 4.37 (m,2H, CH2Ph), 3.95 (s, 4H, THF), 1.96 (s, 4H, THF). 13C NMR(100 MHz CDCl3, ppm): d 152.04 (Ar–O), 137.28 (Ar–C), 128.70(Ar–C), 127.78 (Ar–C), 127.34 (Ar–C), 127.03 (Ar–C), 126.96 (Ar–C), 124.92 (Ar–Cl), 122.55 (Ar–C), 117.16 (Ar–C), 69.47 (THF),45.36 (CH2Ph), 25.37 (THF). 31P{1H} NMR (161 MHz CDCl3, ppm):d 13.62. Anal. Calc. for C17H23ClNO5P: C, 52.65; H, 5.98; N, 3.61.Found: C, 52.45; H, 6.37; N, 3.99%.

2.6.4. [4-MeC6H4OP(O)O(OH)][BnNH3] (15)The compound 15 was synthesized from 9 (0.10 g, 0.27 mmol)

and ZnCl2 (37 mg). Yield = 42 mg (70%). IR (neat, cm�1): 3302 (N–H), 1202 (P@O), 694 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d7.31–7.28 (m, 9H, ortho, meta, para), 4.18 (m, 2H, CH2Ph), 3.90 (s,5H, THF and OH), 2.30 (s, 3H, Ar–Me), 1.92 (s, 4H, THF). 13C NMR(100 MHz CDCl3, ppm): d 148.64 (Ar–O), 142.30 (Ar–C), 138.47(Ar–Me), 135.12 (Ar–C), 130.40 (Ar–C), 128.78 (Ar–C), 127.56(Ar–C), 120.18 (Ar–Me), 69.13 (THF), 45.25 (CH2Ph), 25.52 (THF),20.81 (Ar–Me). 31P{1H} NMR (161 MHz CDCl3, ppm): d 13.44. HRMS(ESI) for C14H18NO4P (M+THF)+: Calc., 367.1549; Found: 367.1548.

2.6.5. [4-t-BuC6H4OP(O)O(OH)][BnNH3] (16)The compound 16 was synthesized from 10 (0.10 g, 0.24 mmol)

and ZnCl2 (33 mg). Yield = 58 mg (70%). IR (neat, cm�1): 3316 (N–H), 1211 (P@O), 695 (P–N). 1H NMR (400 MHz, CDCl3, ppm): d7.34–7.04 (m, 9H, ortho, meta, para), 4.22 (m, 2H, CH2Ph), 3.89 (s,5H, THF and OH), 1.90 (s, 4H, THF), 1.29 (s, 9H, Ar–CMe3). 13CNMR (100 MHz CDCl3, ppm): d 148.14 (Ar–O), 147.89 (Ar–C),138.67 (Ar–CMe3), 138.42 (Ar–C), 128.73 (Ar–C), 127.54 (Ar–C),126.79 (Ar–C), 119.70 (Ar–C), 68.30 (THF), 45.19 (CH2Ph), 34.46(Ar–CMe3), 31.48 (Ar–CMe3), 25.68 (THF). 31P{1H} NMR (161 MHzCDCl3, ppm): d 13.66. HRMS (ESI) for C17H24NO4P (M+THF)+: Calc.,409.2018; Found: 409.2016.

2.6.6. [Me2NP(O)O(OH)][Me2NH2] (17)HMPA (0.10 g, 0.56 mmol) and ZnCl2 (76 mg) were used.

Yield = 70 mg (75%). IR (neat, cm�1): 3360 (N–H), 1181 (P@O). 1HNMR (400 MHz, CDCl3, ppm): d 3.89 (s, 4H, THF), 2.62 (br, 12H,NMe), 1.89 (s, 4H, THF). 13C NMR (100 MHz CDCl3, ppm): d 69.13(THF), 36.78 (NMe), 25.36 (THF). 31P{1H} NMR (161 MHz CDCl3,ppm): d 27.85. Anal. Calc. for C8H23N2O4P: C, 39.66; H, 9.57; N,11.56. Found: C, 40.01; H, 9.39; N, 11.41%.

Table 1Crystal data for the structures 10 and 15.

Compound 10 15

Empirical formula C48H58N4O4P2 C28H36N2O8P2

Formula weight 816.92 590.53Crystal system monoclinic monoclinicSpace group P21/c P21/cT (K) 173 173Wavelength (Å) 0.71073 0.71073a (Å) 20.8933(8) 12.9529(8)b (Å) 9.8712(3) 6.5937(4)c (Å) 22.5314(8) 17.3840(11)a (�) 90 90b (�) 99.200(10) 90.443(3)c (�) 90 90V (Å3) 4587.1(3) 1484.68(16)Z 4 2Dcalc (g cm�3) 1.183 1.321Reflections collected 31 921 10 463Number of independent

reflections11 178 3620

Goodness-of-fit (GOF) 1.016 0.979Final R indices [I > 2r(I)] R1 = 0.0505,

wR2 = 0.1358R1 = 0.0499,wR2 = 0.1293

R indices (all data) R1 = 0.0914,wR2 = 0.1676

R1 = 0.0814,wR2 = 0.1563

R1 =P

|Fo| � |Fc|/P

|Fo|, wR2 = [P

(F2o � F2

c )2/P

w(F2o)2]1/2.

P. Malik et al. / Polyhedron 29 (2010) 2142–2148 2145

2.7. X-ray crystallography

Single crystals of 10 and 15 suitable for structural studies wereobtained by crystallization from 1:1 methylene chloride/hexanemixture at 0 �C over a period of one week. X-ray data collectionwas performed with Bruker AXS (Kappa Apex 2) CCD diffractome-ter equipped with graphite monochromated Mo (Ka) (k = 0.7107 Å)radiation source. The data were collected with 100% completenessfor h up to 25�. x and u scans were employed to collect the data.The frame width for x was set to 0.5� for data collection. Theframes were integrated and data were reduced for Lorentz andpolarization corrections using SAINT-NT. The multi-scan absorptioncorrection was applied to the data set. All structures were solvedusing SIR-92 and refined using SHELXL-97 [39]. The crystal data aresummarized in Table 1. The non-hydrogen atoms were refinedwith anisotropic displacement parameter. All the hydrogen atomscould be located in the difference Fourier map. The hydrogenatoms bonded to carbon atoms were fixed at chemically meaning-ful positions and were allowed to ride with the parent atom duringrefinement.

3. Results and discussion

3.1. Synthesis and characterization

The phosphodichloridates (1–5) were synthesized by heatingvarious phenols with excess POCl3 in the presence of catalyticamount of lithium chloride under reflux conditions (Scheme 1).

4 POCl3 + ArOHLiCl (cat.)

2-MeC6H42-FC6H42-ClC6H44MeC6H44-tBuC6H4

12345

P

O

ArOCl Cl

Ar =

Scheme 1. Synthesis of phosphodichloridates.

These were isolated in moderate yields as colorless viscous liq-uids after distilling off the excess POCl3. The 1H NMR of 1–5 con-tains the signals for all moieties in the required ratio. 13C NMRreveals that the phenyl carbon atom directly bonded to oxygen isconsiderably deshielded with respect to the other aromatic peakswith the exception of 2 where the aromatic carbon atom attachedto fluorine is even further deshielded. These compounds showedonly one signal in their 31P{1H} NMR as expected from the struc-ture. GC–MS spectra recorded on these compounds reveal themolecular ion peaks as a proton adduct. Finally, their purity wasassured through the correct elemental analysis values. Reliable IRspectra could not be obtained as a result of the sensitivity of thesecompounds to moisture. These compounds have been reported inthe literature previously where some were prepared by the reac-tion of the sodium phenolate salt with POCl3 [40] or reaction ofthe phenol with POCl3 in the presence of an acid scavenger likeEt3N [41] or direct reaction of phenol with POCl3 in the presenceof NaCl [42]. Our contribution has been in the establishment of areliable synthetic route and thorough unambiguous characteriza-tion of these compounds by various spectroscopic methods.

The N,N0-dibenzylphosphorodiamidate derivatives (6–10) weresynthesized by reacting the corresponding aryl phosphorodichlori-date (1–5) with benzyl amine in toluene (Scheme 2). These com-pounds were isolated in 50–70% yield after work up and columnchromatography as white solids.

The IR spectra of 6–10 reveal peaks due to mN–H, mP@O and mP–N

with prominent intensities. The 1H NMR of 6–10 reveals all the ex-pected signals in the correct ratio of integration. The benzylic pro-tons appear as a complex multiplet in 6–10 as a result of couplingwith the neighboring –NH proton and phosphorus with 2JP–

N = 11.9 Hz [43]. The aromatic signals of these compounds in the13C NMR have resemblance to their parent phosphodichloridates.The 31P{1H} NMR of these 6–10 reveal a single peak at ca.11 ppmthat is downfield shifted ca. 8 ppm with respect to the parent phos-phodichloridates compounds. The structural identity and the pur-ity of these compounds were determined using HRMS analysis.The unambiguous structural analysis was performed by measuringthe single crystal X-ray structure of 10. In a similar manner, com-pound 11 was synthesized using 5 and (±)-a-methylbenzylamine.It is noteworthy to mention that the 1H NMR of this compoundshows two broad signals corresponding to the –NH moiety. Theirauthenticity as –NH protons was confirmed using D2O exchangestudies. The 31P{1H} NMR signal is upfield shifted in comparisonto 6–10. This is attributed as a result of electron donation fromthe methyl group on the a carbon atom.

Our initial studies aimed at exploring the reactions of anhy-drous ZnCl2 with 6–10. These reactions were performed with therigorous exclusion of moisture and air in dry THF at ambient tem-perature. To our surprise, there was no reaction. Such an observa-tion remained consistent when dioxane was used as a solvent andthe reaction mixture were heated to reflux. This observations maybe rationalized by reasoning that the acidity of the –NH proton is

+ 4 BnNH2

2-MeC6H42-FC6H42-ClC6H44MeC6H44-tBuC6H4

678910

Ar =

P

O

ArOCl Cl

P

O

ArOBnHN

NHBn

Scheme 2. Synthesis of N,N0-dibenzylphosphorodiamidate.

2146 P. Malik et al. / Polyhedron 29 (2010) 2142–2148

lower than that of the –OH proton. Interestingly, when such reac-tion mixtures were exposed to air over prolonged periods of time, awhite precipitate appeared. Analysis of such reaction mixturesusing 1H NMR after removal of volatiles clearly revealed that somedefinite change may have taken place. The –NH signal disappearedcompletely. 1H NMR signals corresponding to BnNH2 was seen.These observations prompted us to reinvestigate these reactionsunder ordinary conditions by using regular reagent grade THF thatwas not dried previously and exposing them to air. The initial clear

BnNH3

P

O

ArOBnHN

NHBn

anhyd. ZnCl2anhyd.THF

P

O

ArOBnHN

NHBn

ZnCl2(H2O)XTHF

P

O

ArOHO

O

2-MeC6H42-FC6H42-ClC6H44MeC6H44-tBuC6H4

1213141516

Ar =

-BnNH2

Scheme 3. Reaction of N,N0-dibenzylphosphorodiamidate with ZnCl2.

Table 2Selected bond lengths [Å] and bond angles [�] for compound 10.

P(1)–O(1) 1.477(13)P(2)–O(2) 1.607(14)P(1)–N(1) 1.621(18)P(1)–N(2) 1.620(17)N(1)–P(1)–N(2) 111.91(9)O(1)–P(1)–N(2) 113.76(9)O(1)–P(1)–O(2) 113.80(8)O(2)–P(1)–N(1) 103.57(8)

Fig. 1. Molecular structure of 10; thermal ellip

solution containing the reactants became slightly turbid. The vola-tiles were removed and 1H of the reaction mixture had the samecharacteristics as before. In each case the results were identicalresulting in a puzzle. This mystery was solved by treatment of 9with ZnCl2 and isolating the product. This was subsequently crys-tallized using methylene chloride/hexane mixture at 0 �C and sub-jected to single crystal X-ray diffraction studies. Our understandinghas been depicted in Scheme 3.

It is clear that there is cleavage of the P–N bond which is as-sisted by mild Lewis acid like ZnCl2, leading to the formation ofphosphonic acid. Literature reports such a P–N bond cleavage ini-tiated by strong mineral acids under reflux conditions [44,45]. Itis also believed that the P–N bond can be cleaved using Pd saltswhere the product is not as simple as this [46]. Our method maybe considered superior since the transformation is brought aboutusing an environmentally benign cheap salt like ZnCl2, in the com-plete absence of mineral acids.

Compounds 12–16 were isolated in good yields using theabove method. The spectral characteristics are similar to those ob-served for the N,N0-dibenzylphosphorodiamidate precursors 6–10,respectively.

As an application to this concept we decided to carry out a sim-ilar strategy with HMPA with the hope of cleaving the P–N bond.To our surprise, we found that the concept was viable and the ex-pected acid [Me2NP(O)O(OH)][Me2NH2] (17) was isolated in goodyield. This method may be considered a way to detoxify HMPA.This hydrolysis works equally well with other halide salts of zinclike ZnBr2 but we preferred ZnCl2 because of its lower cost and easeof availability. The reaction with other transition-metal divalentcations like Cu2+, Mn2+ and Ni2+ is extremely slow and appreciableproduct could not be isolated under comparable conditions withZnCl2.

soids were drawn at 30% probability level.

Table 3Selected bond lengths [Å] and bond angles [�] for compound 15.

P(1)–O(1) 1.612(16)P(1)–O(2) 1.562(16)P(1)–O(3) 1.497(16)P(1)–O(4) 1.490(14)O(2)–H(2A) 0.8270(3)O(1)–P(1)–O(2) 106.20(8)O(1)–P(1)–O(3) 103.40(9)O(3)–P(1)–O(4) 118.15(8)O(2)–P(1)–O(4) 107.92(9)

Fig. 2. Molecular structure of 15; thermal ellipsoids were drawn at 30% probability level.

P. Malik et al. / Polyhedron 29 (2010) 2142–2148 2147

3.2. Single crystal X-ray diffraction studies

Among the several compounds synthesized in this study, suit-able crystals for X-ray diffraction studies could be obtained from10 and 15. Single crystals were grown from dilute solutions ofthese compounds in 1:1 methylene chloride/hexane mixture at0 �C over a period of one week. Compound 10 crystallizes in themonoclinic space group P21/c with two molecules in the unit cell.Selected bond lengths and angles are listed in Table 2 and themolecular structure is depicted in Fig. 1.

As seen from the bond lengths and angles, the phosphorus cen-ter is in a distorted pyramidal environment. The P@O bond lengthis slightly shorter than the P–O length. The P–N bonds are nearlyidentical.

Compound 15 crystallizes in the monoclinic space group P21/c.Selected bond lengths and angles are given in Table 3 and themolecular structure is depicted in Fig. 2.

The bond lengths reveal that the lengths of the P@O and P–Omoieties are almost identical suggesting delocalization in thesebonds. The structure of the anion resembles that of a distorted pyr-amid. There is interaction between one of the delocalized P–Obonds and one of the N–H protons of the cation. These are sepa-rated by 1.954(2) Å.

4. Conclusions

In summary, we have developed reliable synthetic routes andcharacterization for the preparation of phosphorodichloridatesand N,N0-dibenzylphosphorodiamidates. These compounds weresynthesized in moderate yields and good purity. We have de-scribed the ZnCl2 assisted cleavage of the P–N bond.

Acknowledgements

This work was supported by Department of Science and Tech-nology New Delhi. The services from the NMR facility purchasedunder the FIST program, sponsored by the Department of Scienceand Technology, New Delhi is gratefully acknowledged. Theauthors thank the Department of Chemistry, Indian Institute of

Technology Madras for providing the single crystal X-ray diffrac-tion facility.

Appendix A. Supplementary data

CCDC 750875 and 750876 contain the supplementary crystallo-graphic data for 10 and 15. These data can be obtained free ofcharge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, orfrom the Cambridge Crystallographic Data Centre, 12 Union Road,Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: de-posit@ccdc.cam.ac.uk. Supplementary data associated with thisarticle can be found, in the online version, at doi:10.1016/j.poly.2010.04.002.

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